EP0531427B1 - Procede et appareil de prelevement par pipette d'un liquide dans un recipient hermetique - Google Patents

Procede et appareil de prelevement par pipette d'un liquide dans un recipient hermetique Download PDF

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Publication number
EP0531427B1
EP0531427B1 EP91911012A EP91911012A EP0531427B1 EP 0531427 B1 EP0531427 B1 EP 0531427B1 EP 91911012 A EP91911012 A EP 91911012A EP 91911012 A EP91911012 A EP 91911012A EP 0531427 B1 EP0531427 B1 EP 0531427B1
Authority
EP
European Patent Office
Prior art keywords
probe
container
axis
closure
orthogonally
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP91911012A
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German (de)
English (en)
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EP0531427A1 (fr
Inventor
Charles Forrest Collier
William G. Di Maio
James L. Seago
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
EIDP Inc
Original Assignee
EI Du Pont de Nemours and Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by EI Du Pont de Nemours and Co filed Critical EI Du Pont de Nemours and Co
Publication of EP0531427A1 publication Critical patent/EP0531427A1/fr
Application granted granted Critical
Publication of EP0531427B1 publication Critical patent/EP0531427B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1079—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices with means for piercing stoppers or septums
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/119163—Automated chemical analysis with aspirator of claimed structure
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Definitions

  • This invention relates to a method and apparatus for pipetting liquids from a sealed container and, more particularly, to a method and apparatus for reducing pressure differences between the interior and exterior of a sealed container, thereby permitting more accurate pipetting of liquids.
  • the resealable lid/container structure which lengthens reagent life, also inhibits the ability of an automated chemical analyzer to accurately remove fluid from the container. This happens because the flexible or elastomeric material used for the lid seals tightly around the pipetting probe or needle when the probe is inside the container. When fluid is removed, a vacuum is produced because the seal does not allow air to enter. This vacuum could adversely affect pipetting performance.
  • This vacuum condition lasts over a period of time, depending on many variables, but has been observed to last for days. So the effect is felt on the immediate aspiration as well as those that which may be performed in the future.
  • the effect of repeated aspirations from the same container can also be additive. Thus each time fluid is removed, the vacuum become greater and greater.
  • Precision of the reagent delivery is also affected by the vacuum. More spread or greater imprecision is observed with the container vacuum. This imprecision is attributed to, among other, gas in the fluid line, varied vacuum levels producing different effects, and bouncing of the fluid miniscus when withdrawing the probe from the container. Such variables are difficult if not impossible to control, so a means of eliminating the vacuum is needed.
  • Averette uses a coaxial probe to aspirate fluid from a sealed vessel. After the probe penetrates the sealing member of the vessel, fluid from the vessel may be aspirated through the inner tube of the coaxial probe to the aspiration tubing. During aspiration, air is vented into the vessel through the vent tubing and down through the outer annulus of the probe to the opening in the side of the coaxial probe. While this is a satisfactory alternative, where cross contamination is a concern the carryover problems can be severe.
  • Ringrose et al. in U.S. Patent 3,872,730 discloses a device for sampling from a closed blood tube such as a "Vacutainer" tube.
  • a dual needle probe penetrates the closure of the tube, allowing the first needle to vent the interior of the tube to atmosphere and the second needle to aspirate fluid from the tube.
  • the double penetration which occurs each time a sample is taken leads to the more rapid deterioration of the integrity of the seal of the container.
  • Uffenheimer U.S. Patent 4,756,201 discloses a device for sampling from a closed blood tube such as a "Vacutainer" tube. Referring to Figure 1 of Uffenheimer, when the probe first enters the tube, through the closure, the shear valve is positioned such that ambient air in the equilibration chamber is allowed to vent into the tube. After venting the shear valve is repositioned to allow the pump to aspirate from the tube.
  • this invention is a method for withdrawing liquid samples from a sealed sample container having an axis, the container having an elastomeric closure lying across the axis, using a robotic aspirating probe, the probe affording degrees of linear motion along the axis and orthogonal to the axis, comprising the steps of: (a) introducing the probe through the closure into the container, (b) moving the probe orthogonally of the axis to stretch the closure, thereby opening a passageway adjacent the probe to atmosphere, (c) applying vacuum to the probe, thereby to aspirate a sample or reagent from the container, and (d) withdrawing the probe from the container, whereby the closure effects aspirating action on the probe, thereby preserving the contents of the container.
  • the probe is returned orthogonally to its axial position prior to performing step (b), i.e., before it is withdrawn from the container.
  • step (b) i.e., before it is withdrawn from the container.
  • step (b) significantly increases the accuracy with which liquids may be pipetted liquids. This is done quite simply by reducing the pressure difference between the inside and outside of the sealed containers, by the simple approach of moving the probe laterally of the axis of the container. No additional mechanical features such as needles, etc. of the invention are necessary.
  • the wiping action provided by the lid of the container removes any droplets which might otherwise contribute to pipetting imprecision.
  • an apparatus for withdrawing liquid samples from a sealed sample container having an axis, the container having an elastomeric closure lying across the axis said apparatus comprising a robotic aspirating probe, said probe providing linear motion along the axis of the container and orthogonal to the axis, means for applying vacuum within the probe, and means to control the motion of the robotic probe, said control means being arranged to cause initial introduction of the probe through the closure into the container, and, subsequently, movement of the probe orthogonally of the axis to stretch the closure, thereby opening a passageway adjacent the probe to atmosphere, followed by application of vacuum within the probe by the means for applying, thereby to aspirate a sample from the container, and withdrawal of the probe from the container, whereby the closure effects aspirating action on the probe, thereby preserving the contents of the container.
  • the apparatus is further improved by the control means which is arranged to cause return of the probe orthogonally to its original position prior to orthogonal movement.
  • the probe desirably is provided with an outer diameter of the
  • FIG. 1 is a diagrammatic view, partially in cross section, partially in block, depicting a pipette constructed in accordance with this invention.
  • FIG. 1 apparatus constructed in accordance with this invention which serves to reduce any vacuum or pressure present in a sealed sample container 10 so that liquids may be pipetted from the container with a high degree of accuracy.
  • the container 10 is conventional may be constructed of any suitable material which is typically used for such purposes. Such containers are available on the open market and need only the chemically inert.
  • the container 10 has a seal or closure lid 12 at the top thereof which again may be any suitable material. Although not at all critical, it is preferred that the containers used have a closure of the type sold with Du Pont's Dimension® Clinical Chemistry System (E. I. du Pont de Nemours and Company).
  • Such containers have an elastomeric closure 12 which comprises an elastomeric layer of suitable material, such as silicon rubber, covering a three ply laminate of a polyester film, a polyvinylidene chloride layer, and a polypropylene sheet.
  • elastomeric layer of suitable material such as silicon rubber
  • the laminate reduced evaporation and the elastomeric layer is self healing and effects a "squeegee" action to wipe the probe.
  • a similar laminate is described in the DeBenedictis application.
  • the particular lid structure used is not important so long as it is elastomeric, as will be described.
  • a probe 14 adapted to penetrate the lid 12 of the container 10 along the container axis 16 is attached through a tubing 18 to a vacuum pump 20.
  • the probe 14 is hollow and is supported coaxially by a sleeve 22 secured thereabout and mounted in a holder 24.
  • the sleeve and probe may be formed of any suitable material such as stainless steel.
  • the holder 24 in turn 24 is adapted to be moved in an XZ sense (horizontal and vertical) through a linkage 26 by a servo drive 28 which is controlled by a controller 30.
  • the pump 20 is also controlled by the controller 30.
  • the controller 30 may be any of the conventional controllers using microprocesser chips or otherwise. Any suitable robotic controller that may be sued for this invention.
  • the controller may be that sold by E. I. du Pont de Nemours and Company for use on their Dimension® System. Any other controllers are suitable for this purpose provided only that they have the ability to provide lateral and vertical movement of the probe with approximately three to four pounds force.
  • the probe 14 is initially positioned slightly off center of the axis 16 of the container 10. The amount of this offset will vary with the materials used and the diameter of the lid and the size of the probe, but typically may be in the order 0.2 cm. Under the control of the controller 30 (FIG. 1), the probe 14 is moved downward to penetrate the lid 12 of the container 10. The downward movement of the probe is stopped just before the tip 34 of the sleeve 22 touches the lid 12. Typically this clearance can be in the order of 0.015 cm to avoid contaminating the support sleeve with the reagent.
  • the probe 14 is moved laterally to lie on the axis of the container 16. This stretches the elastomeric portion of the lid 12 sufficiently to allow air to leak through the distended opening in the lid and thereby to allow the pressure within the container 10 to equilibrate with that on the outside of the container, i.e., atmosphere.
  • the lateral movement of the probe also tears the film layers which constitute a part of the elastomeric lid.
  • Many lids were effectively vented with as little as 0.010 cm sideways motion. However, in order to ensure adequate venting, a typical sideways movement of 0.020 cm was used as a failsafe procedure. Of course with different thickness lids more or less sideways motion may be needed in order to provide an adequate "leak" about the needles to vent the container.
  • FIG. 1 illustrates this by 40 which may be holder for the container.
  • the holder is attached to a rigid support 42.
  • the holder may be a ring, clamp, or any other mechanism which prevents lateral movement of the container. While movement of the probe to the centerline of the container, i.e., the axis, is preferred, the probe movement may be chordal or radially out as desired. Movement to the axis generally accomodates the greatest probe depth.
  • the pump 20 is actuated by the controller and the contents of the container 10 aspirated to achieve the sampling desired. This aspiration takes place during the period of time that the vent formed by distending the elastomeric lid 12 is open to form the "vent".
  • the probe is returned to its original position relative to the axis 16 by a return orthogonal or lateral movement. Finally the probe is withdrawn from the container.
  • the mechanism just described facilitates a relatively simple method and provides an apparatus for venting a sealed sample container to atmosphere. It requires no additional venting needles, parts or mechism. It requires no additional valves in the system or otherwise and yet it achieves relatively high accuracy in sampling volumes.

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  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Accessory Devices And Overall Control Thereof (AREA)
  • Facsimiles In General (AREA)

Abstract

On introduit une sonde (14) par le couvercle élastomère (12) d'un récipient (10) d'échantillon fermé puis on la déplace latéralement afin de tendre le couvercle (12) et ainsi de ménager un passage d'air vers l'atmosphère tandis que l'on aspire l'échantillon.

Claims (12)

  1. Une méthode d'aspiration d'échantillons liquides à partir d'un conteneur hermétiquement clos ayant un axe et ledit conteneur ayant un obturateur en matériau élastomère disposé perpendiculairement par rapport audit axe de conte- neur, ladite méthode utilisant une sonde d'aspiration robotisée, ladite sonde ayant des possibilités de mouvement liné aire restreint le long dudit axe de conteneur et perpendi- culairement audit axe de conteneur et comprenant les phase suivantes:
    (a) introduction de ladite sonde à l'intérieur du conteneur, au travers de l'obturateur,
    (b) mouvement de la sonde perpendiculairement à l'axe du conteneur pour étirer l'obturateur et, de ce fait, ouvrir un passage contigu à la sonde pour la mise à l'atmos- phère du conteneur,
    (c) application d'un vide à l'intérieur de la sonde pour créer un effet d'aspiration de l'échantillon de liquide conservé dans le conteneur, et
    (d) retrait de la sonde du conteneur, accompagné d'un effet d'aspiration de l'obturateur sur la paroi de la sonde, ce qui a pour effet de préserver le liquide conservé à l'intérieur du conteneur.
  2. La méthode selon la revendication 1, qui comporte aussi une phase supplémentaire de la sonde le long de l'axe dudit conteneur et perpendiculairement audit axe pour ramener ladite sonde à la position qu'elle occupait initialement avant la mise en oeuvre de la phase (b).
  3. La méthode selon la revendication 2, dans laquelle la sonde est maintenue pour éviter toute flexion.
  4. La méthode selon la revendication 1, dans laquelle la sonde est maintenue pour éviter toute flexion.
  5. La méthode selon la revendication 1, dans laquelle la sonde est introduite dans le conteneur le long de l'axe dudit conteneur.
  6. La méthode selon la revendication 5, qui comporte la phase supplémentaire de ramener la sonde perpendiculairement à sa position axiale avant la phase (b).
  7. La méthode selon la revendication 6, dans laquelle la sonde est maintenue pour éviter toute possibilité de flexion.
  8. Un appareil pour aspirer des échantillons de liquide d'un conteneur d'échantillonnage hermétiquement clos ayant un axe de conteneur, ledit conteneur ayant un obturateur en matériau élastomère disposé perpendiculairement par rapport audit axe de conteneur, ledit appareil comprenant une sonde aspirante robotisée, ladite sonde ayant des possibilités de mouvement linéaire le long de l'axe dudit conteneur et perpendiculairement par rapport à cet axe, un moyen pour appliquer le vide à l'intérieur de la sonde et un moyen pour commander le mouvement de la sonde robotisée, ledit moyen de commande étant conçu pour forcer l'introduction initiale de la sonde dans le conteneur au travers de l'obturateur et, ensuite, le mouvement de la sonde perpendiculairement par rapport à l'axe dudit conteneur pour étirer ledit obturateur et ouvrir de cette façon un passage de mise à l'atmosphère contigu à ladite sonde, et ensuite application du vide à l'intérieur de la sonde à l'aide du moyen d'aspiration d'échantillon de liquide du conteneur, et ensuite retrait de ladite sonde du conteneur avec effet d'aspiration par l'obturateur sur la sonde ce qui, de cette façon, préserve le liquide conservé dans le conteneur.
  9. L'appareil selon la revendication 8, dans lequel le moyen de commande est étudié pour ramener la sonde à sa position d'origine par rapport à l'axe du conteneur par mouvement perpendiculaire par rapport audit axe du conteneur.
  10. L'appareil selon la revendication 9, dans lequel la sonde est cylindrique et partiellement entourée d'un manchon coaxial placé autour de ladite sonde.
  11. L'appareil selon la revendication 10, dans lequel le mouvement perpendiculaire est au moins de 0,1 cm.
  12. L'appareil selon la revendication 10, dans lequel l'enveloppe de la sonde a la possibilité de s'approcher de 0,2 cm de l'obturateur avant tout mouvement perpendiculaire de la sonde.
EP91911012A 1990-05-25 1991-05-20 Procede et appareil de prelevement par pipette d'un liquide dans un recipient hermetique Expired - Lifetime EP0531427B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US528357 1983-08-31
US07/528,357 US5130254A (en) 1990-05-25 1990-05-25 Method for pipetting liquid from a sealed container
PCT/US1991/003326 WO1991019181A1 (fr) 1990-05-25 1991-05-20 Procede et appareil de prelevement par pipette d'un liquide dans un recipient hermetique

Publications (2)

Publication Number Publication Date
EP0531427A1 EP0531427A1 (fr) 1993-03-17
EP0531427B1 true EP0531427B1 (fr) 1994-04-13

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EP91911012A Expired - Lifetime EP0531427B1 (fr) 1990-05-25 1991-05-20 Procede et appareil de prelevement par pipette d'un liquide dans un recipient hermetique

Country Status (6)

Country Link
US (1) US5130254A (fr)
EP (1) EP0531427B1 (fr)
JP (1) JP2511606B2 (fr)
CA (1) CA2083489A1 (fr)
DE (1) DE69101706T2 (fr)
WO (1) WO1991019181A1 (fr)

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US5795784A (en) 1996-09-19 1998-08-18 Abbott Laboratories Method of performing a process for determining an item of interest in a sample
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US6716396B1 (en) * 1999-05-14 2004-04-06 Gen-Probe Incorporated Penetrable cap
US20080148872A1 (en) * 2000-05-12 2008-06-26 Gen-Probe Incorporated Method for accessing the contents of an assembly
US6817256B2 (en) * 2001-02-27 2004-11-16 Alfa Wassermann, Inc. Pipette sampling system
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US7396512B2 (en) 2003-11-04 2008-07-08 Drummond Scientific Company Automatic precision non-contact open-loop fluid dispensing
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US8864725B2 (en) 2009-03-17 2014-10-21 Baxter Corporation Englewood Hazardous drug handling system, apparatus and method
JP4936235B2 (ja) 2009-12-21 2012-05-23 株式会社日立プラントテクノロジー 発光測定装置の試薬開封機構および試薬開封機構における開封針制御方法
US9039992B2 (en) 2011-06-06 2015-05-26 Abbott Laboratories Apparatus for closed tube sampling and open tube sampling for automated clinical analyzers
EP2784516A4 (fr) * 2011-11-25 2015-08-26 Toppan Printing Co Ltd Embout de pipette prévu pour être utilisé dans un dispositif de distribution et procédé de perforation d'un film de cartouche de réactif utilisant ce dernier
US9213043B2 (en) 2012-05-15 2015-12-15 Wellstat Diagnostics, Llc Clinical diagnostic system including instrument and cartridge
US9625465B2 (en) 2012-05-15 2017-04-18 Defined Diagnostics, Llc Clinical diagnostic systems
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JP6318595B2 (ja) * 2013-12-12 2018-05-09 東ソー株式会社 試料吸引装置
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Also Published As

Publication number Publication date
JPH05509158A (ja) 1993-12-16
WO1991019181A1 (fr) 1991-12-12
EP0531427A1 (fr) 1993-03-17
DE69101706T2 (de) 1994-08-04
CA2083489A1 (fr) 1991-11-26
DE69101706D1 (de) 1994-05-19
US5130254A (en) 1992-07-14
JP2511606B2 (ja) 1996-07-03

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